|Publication number||US6216023 B1|
|Application number||US 09/218,876|
|Publication date||Apr 10, 2001|
|Filing date||Dec 22, 1998|
|Priority date||Dec 22, 1998|
|Also published as||WO2000036972A1|
|Publication number||09218876, 218876, US 6216023 B1, US 6216023B1, US-B1-6216023, US6216023 B1, US6216023B1|
|Inventors||Bo Holte, Michael Mythen|
|Original Assignee||Instrumentarium Corp.|
|Export Citation||BiBTeX, EndNote, RefMan|
|Patent Citations (4), Non-Patent Citations (3), Referenced by (5), Classifications (14), Legal Events (7)|
|External Links: USPTO, USPTO Assignment, Espacenet|
The present invention relates to improved methods and apparatus for determining differences between CO2 levels in a specific organ or region of the body of a mammalian subject and systemic CO2 levels in the blood of the subject.
Regional CO2 measurements are typically obtained from the mucosa or other tissue found in an organ or region of the body, for example, the gastrointestinal tract or urinary bladder. One way of obtaining such measurements is to place a tonometric catheter having a sampling chamber permeable to CO2 in a hollow organ of the body, such as the stomach or intestine, so that the sampling chamber is contiguous with the mucosa of the gut. A fluid sampling medium is supplied to the sampling chamber through a tube. The sampling medium receives CO2 which passes from the mucosa into the sampling chamber. The sampling medium is then removed from the chamber through the tube and the regional CO2 level is measured by suitable gas analysis means. See for example published PCT application PCT/US94/02953 and corresponding U.S. national stage application Ser. No. 08/433,398, filed May 18, 1995 describing catheters of this type and their uses. The measurement is typically expressed as a regional CO2 partial pressure (PrCO2).
Regional tonometric measurements provide an indication of the condition of the organ. It is becoming more fully appreciated that tonometric measurements, such as gastrointestinal measurements, can be used to provide an early indication or warning of serious physiological conditions which may be difficult to otherwise diagnose. Such conditions include dysoxia (deficiency in oxygen delivery), hypovolemia (abnormally decreased volume of circulating fluid in body), sepsis, and shock. The early indication arises from the fact that the gastrointestinal tract is the first organ of the body to be affected by such a condition as reflected in reduced mucosal perfusion (blood flow) in the gastrointestinal tract. The reduced perfusion in turn, increases the regional CO2 partial pressure. Since the altered CO2 partial pressure can be ascertained tonometrically, tonometric monitoring is particularly valuable in surgical recovery units, intensive care units, and other settings. See for example, “The Role of Gut Mucosal Hyperfusion in the Pathogenesis of Post-operative Organ Dysfunction” by M. G. Mythen and A. R. Webb, Intensive Care Medicine (1994), 20:203-209 and “Gastric Intramucosal pH: A Non-invasive Measurement for the Indirect Measurement of Tissue Oxygenation” by Cinda H. Clark and Guillermo Gutierrez in American Journal of Critical Care (1992), 2:53-60.
A convenient and straightforward indication of the state of gut mucosal perfusion is the difference between a regional CO2 partial pressure measurement (PrCO2) obtained tonometrically from the organ and the systemic CO2 partial pressure, for example, that existing in arterial blood (PaCO2). See the PCT patent application and the Mythen et al. article, supra. Venous blood CO2 partial pressure (PvCO2) can also be used. An increase in the CO2 partial pressure difference, or the “CO2 gap”, between the regional and systemic CO2 levels indicates a reduction in the adequacy of gut mucosal perfusion and the onset of dysoxia and/or other conditions hazardous to the patient.
The CO2 level of arterial blood is typically measured by periodically drawing a blood sample from the patient into a cuvette. The cuvette is then carried to, and placed in, a blood gas analyzer that uses, for example, electrochemical sensors, to measure the partial pressure of the sample. Or, a probe may be placed in an artery of the patient to obtain blood samples.
Because electrochemical sensors are temperature sensitive and because the temperature of the blood sample will change during transport to the blood gas analyzer, it has become conventional to correct blood CO2 partial pressure measurements to a standard temperature. Also, the blood CO2 partial pressure will vary with the temperature of the subject. For example, if the body temperature of the subject is reduced from the usual body temperature, a decrease in the partial pressure PaCO2 will occur, for a given amount of CO2 in the blood.
The use of a standard temperature permits data periodically obtained from a patient to be meaningfully compared even though the temperature of the patient changes in the course of time or permits data from a given patient to be compared to data obtained from other patients or compared to recognized criteria. Standard temperature arterial CO2 partial pressure values avoid confusion, as when a patient is attended by a number of physicians. For the foregoing reasons, use of standard temperature blood CO2 partial pressure values has become an accepted medical protocol. The standard temperature is typically 37° (98.6° F.), the normal temperature of the human body. The blood gas analyzer contains thermal control apparatus to ensure that the blood sample is at the standard temperature when the measurement of PaCO2 is made and contains a correction algorithm to correct the measurement to the actual temperature.
Recently, the use of gas as the tonometric sampling medium has come into use. Air may be used for this purpose. A gas analysis means, such as an infrared spectrometer, is connected directly to the tonometric catheter. The gaseous sampling medium is withdrawn from the sampling chamber of the tonometric catheter and passed through the gas analysis means, such as an infrared spectrometer, connected to the catheter to determine the regional CO2 partial pressure. The sampling medium withdrawn from the tonometer is at the existing actual temperature of the organ, which is usually the body temperature of the subject, and the regional CO2 partial pressure determination is thus made at that temperature.
The tonometrically obtained regional CO2 partial pressure (PrCO2) is compared to the arterial CO2 partial pressure (PaCO2) to determine the CO2 gap. This is currently done notwithstanding the fact that the regional CO2 partial pressure is an actual body temperature value whereas the arterial CO2 partial pressure is a standard temperature value. This use of values obtained for two different temperatures introduces the possibility of error in the determination of the CO2 gap.
For a normal person, the standard and actual body temperatures are the same (both 37° C.) so that any errors are small or non-existent. But, actual body temperatures vary, and can vary over a wider range than is often appreciated. Fevers increase the actual body temperature above 37° C., for example to 40° C. (104° F.). In many medical procedures, the temperature of a patient is deliberately reduced to slow metabolic functions, reduce swelling, or for other reasons. Reductions to a temperature of 30° C. (86° F.) may occur. Greater differences between actual body temperature of the subject and the standard temperature correspondingly increase the error in the determination of the regional-arterial CO2 partial pressure gap. These errors may result in inappropriate diagnosis and/or treatment of the subject.
The invasive and intermittent nature of obtaining direct arterial CO2 partial pressure measurements by periodically drawing blood or using probes has led to determining systemic CO2 levels non-invasively and continuously by using the exhaled respiration gases of the patient. Typically, the CO2 level existing at the end of exhalation, the end-tidal level (EtCO2), is used for this purpose. The end-tidal determination is carried out at actual body temperature.
In normal persons, the use of end tidal CO2 measurements in lieu of arterial blood CO2 measurements is usually appropriate since the gradient between the two is low and constant so that it is possible to determine the CO2 gap by a comparison of PrCO2 and PetCO2. However, for many persons, or for subjects in particular circumstances, such as mechanically ventilated patients, the correlation between PetCO2 and PaCO2 is lower. Further, unless the standard temperature PaCO2 value is compensated for the actual temperature of the subject, the gradient between PetCO2 and PaCO2 will change as the temperature of the subject changes. See “The Arterial to End-Tidal Carbon Dioxide Gradient Increases with Uncorrected PaCO2 Determination During Mild to Moderate Hypothermia”, Christian Sitzwohl et al., Anesthesia Analc 1998; 86.
Concern over the use of end tidal CO2 for the foregoing reasons and/or a preference for a particular blood gas analysis protocol has lead some medical practitioners to prefer standard temperature blood gas analysis CO2 values, while others use actual temperature blood gas analysis values, while others use end-tidal CO2 values. This has, correspondingly, made obtaining CO2 gap measurements that are understood by, and acceptable to, medical practitioners difficult and has detracted from full realization of the usefulness of such measurements.
It is, therefore, the object of the present invention to provide methods and apparatus for providing an improved regional-systemic CO2 partial pressure gap measurement for use in diagnostic, treatment or other purposes.
More particularly, it is an object of the present invention to provide methods and apparatus for providing an accurate indication of the regional-artetial CO2 partial pressure gap and in which errors arising from the use of values reflecting CO2 partial pressures obtained at different temperatures are eliminated.
A further object of the present invention is to provide such methods and apparatus which permit the use of end tidal CO2 partial pressures to determine the CO2 gap.
Various other features, objects, and advantages of the invention will be made apparent from the following detailed description and the drawings.
FIG. 1 is a simplified showing of the apparatus of the present invention which may be utilized to carry out the method of the present invention;
FIG. 2 is a simplified block diagram showing the steps of the method of the present invention;
FIG. 3 is a block diagram showing further details of the method shown in FIG. 2; and
FIG. 4 is a block diagram showing the steps in an embodiment of the method of the present invention in which an end tidal CO2 partial pressure value is employed.
In the method and apparatus of the present invention, it is necessary to obtain a systemic CO2 partial pressure value as shown in step 10 in FIG. 2. To this end, a sample of arterial blood is withdrawn from the subject, for example through an arterial catheter into a preheparinized syringe 200 shown in FIG. 1. See step 11 in FIG. 3. The barrel of the syringe may be used as a cuvette or the sample may be transferred to a separate cuvette. The cuvette is then transported to and placed in conventional blood gas analysis equipment 202 where the arterial CO2 partial pressure (PaCO2) is determined, as by using electrochemical electrodes. In accordance with conventional practice, the blood gas analysis equipment 202 typically employs temperature control apparatus to establish and maintain the blood sample being analyzed at a standard temperature so as to provide a standard temperature arterial CO2 partial pressure value at step 12. Under current medical protocols, the standard temperature is 37° C.
Or, if the blood sample is not at the standard temperature, the blood gas analyzer may carry out a computational temperature correction to provide a standard temperature value. For this purpose, the temperature of the sample is determined. The output of the blood gas analyzer is corrected in accordance with the temperature differences at step 13 to provide a blood CO2 partial pressure measurement (PaCO2) at the standard temperature.
With some blood gas analyzers currently in use the actual body temperature of the subject, as measured in step 14 can be entered to provide a reading of blood CO2 partial pressure (PaCO2) comprising that for the actual body temperature. See step 15.
To obtain the regional CO2 partial pressure in step 20, a tonometric catheter 204 is placed in or adjacent the organ of interest. As noted above, such a catheter has a hollow sampling chamber 206 that is permeable to CO2. A tube 208 extends from the chamber to outside the body of the patient. The distal end of the tube is connected to a sampling chamber. The proximal end of the tube is connected to the gas input connection of apparatus for measuring CO2 levels in gaseous media. Such apparatus is typically capnograph 210. The capnograph made and sold by the Datex-Ohmeda division of Instrumentarium Corp., Helsinki, Finland under the trademark “Tonocap” can be used as capnograph 210. Capnograph 210 contains microprocessor or other circuitry suitable for carrying out steps of the present invention. Means, such as a pump, are provided in capnograph 210 to inflate the sampling chamber with a gaseous sampling medium, such as air, through tube 208. The sampling medium receives CO2 passing from the organ into the sampling chamber. After a period of time sufficient to allow the level of CO2 in the sampling medium to equilibrate with the CO2 level in the organ of interest, the pump is operated to draw the gaseous sampling medium out of sampling chamber 206 into capnograph 210 where the gaseous sampling medium containing the CO2 is analyzed, typically by an infrared spectrometer, to determine the concentration of CO2 in the sampling medium. The value so determined is corrected for ambient atmospheric pressure to arrive at a regional CO2 partial pressure (PrCO2). The sampling cycle is then usually repeated at preset intervals.
It will be appreciated that since sampling chamber 206 of tonometric catheter 204 is in or adjacent to the organ of interest, the measurement of regional CO2 partial pressure value (PrCO2) will be that for the actual temperature of the organ.
A capnograph 210 suitable for use in the present invention allows entry of a systemic CO2 partial pressure value, for example, the arterial blood (PaCO2) value obtained from the blood gas analyzer, as at key pad 212. The operator also inserts an indication of whether the systemic CO2 partial pressure from step 10 is that for the standard temperature or in that for the actual body temperature of the subject. See step 22.
If the systemic CO2 partial pressure value is that for the actual body temperature of the subject, this partial pressure value is compared directly with the regional CO2 partial pressure (PrCO2) value at step 24. The CO2 “gap” difference or measurement obtained from the comparison is provided at step 26. In FIG. 2, the step paths 28 and 30 lead to value comparison step 24.
If, as is often the case, the systemic CO2 partial pressure, for example, an arterial value, is that for the standard temperature, the step path becomes that indicated by 32. The actual temperature of the subject, measured at step 14, is inputted into capnograph 210. A correction is then carried out at step 34 a or 34 b to alter one of the systemic CO2 partial pressure (PaCO2) (step 34 a) or the regional CO2 partial pressure (PrCO2) (step 34 b) so that both CO2 partial pressure values are those representative of CO2 partial pressures at a common temperature.
For example, if it is desired to correct a standard temperature arterial CO2 partial pressure value (PaCO2) to that of the actual temperature of the subject as in step 34 a, an algorithm suitable for this purpose is PCO2 (T)=PCO2 (37°)×100.019×(T−37) where T in the exponent is the actual temperature of the subject. A corresponding algorithm may be derived if it desired to correct the actual body temperature regional CO2 partial pressure to a standard temperature value in alternative step 34 b. In carrying out the present invention, it is presently seen as preferred to correct the actual body temperature regional CO2 partial pressure at step 34 b to a standard temperature value.
With one of the systemic CO2 value or PrCO2 value corrected so that both values represent CO2 partial pressures at a common temperature, i.e. the standard temperature or the actual body temperature, the systemic CO2 partial pressure, as represented by the PaCO2 value, and the regional CO2 partial pressure PrCO2 are compared at step 36 to produce the difference comprising the CO2 gap at step 26. The use of common temperature CO2 partial pressure values insures that the resulting CO2 gap determination is an accurate, medically useful measurement.
FIG. 4 shows the steps of a method in which the end tidal CO2 partial pressure value (PetCO2) is also obtained, as at step 40. As noted above, use of end tidal CO2 values as an indication of systemic CO2 partial pressures is advantageous in that it is non-invasive and continuous but may not always accurately indicate the actual systemic CO2 partial pressure, as reflected in the arterial blood (PaCO2). To obtain the end-tidal CO2 partial pressure value, a breathing mask or endotracheal tube is provided for the subject and connected via a breathing circuit to a mechanical ventilator. A side stream sample of the breathing gases can be removed from the breathing circuit in conduit 212 and supplied to capnograph 210 for determination of the end tidal CO2 partial pressure (PetCO2) value. Or a main-stream sensor may be placed in the breathing circuit for determining the end tidal CO2 partial pressure value (PetCO2), and for providing a signal corresponding to same to capnograph 210. The end tidal CO2 partial pressure value will be that for the temperature of the lungs of the subject. This will normally be the same as the temperature of the organ containing the tonometric catheter due to the uniform body temperature produced by homeostasis that characterizes mammalian subjects.
In the method of FIG. 4, in the event that the arterial CO2 partial pressure value is that corresponding to standard temperature, the correction carried out in step 41, to reflect the actual temperature of the subject is either to correct the standard temperature value of the blood partial pressure value (PaCO2) to an actual temperature value or to correct the end tidal CO2 partial pressure value to standard temperature value. Thus, the PetCO2 value can be changed to a standard temperature value or the PaCO2 value can be changed to an actual body temperature value.
In the method of FIG. 4, it is then necessary to determine whether or not end tidal CO2 partial pressure values can be used as the indication of systemic blood CO2 partial pressure values for determining the CO2 gap. To this end, in step 42, it is necessary to compare the blood CO2 partial pressure value (PaCO2) and the end tidal CO2 partial pressure value (PetCO2) that are now on a same-temperature basis. If there is a high correlation between the two values, that is, if there is a small difference between the two, it is preferable to use end tidal CO2 values for the reasons given above. If there is not a high correlation, or if other circumstances require, the arterial CO2 partial pressure value obtained from blood gas analyzer 102 may be employed. The appropriate one of blood CO2 partial pressure value or the end tidal CO2 partial pressure value is then selected at step 43 for use as the systemic CO2 partial pressure value in the remaining steps of the method shown in FIG. 2.
The above description includes the correction of either blood CO2 partial pressure and/or regional CO2 partial pressure (PrCO2), as in the method of FIGS. 2 and 3, or additional correction of end-tidal CO2 value, as in the embodiment shown in FIG. 4, so that the comparison of steps 24 and 36 are made on a same temperature basis. However, with the appropriate algorithm, it could also be possible to obtain the CO2 gap at step 26 and if the systemic CO2 partial pressure value obtained from the blood sample or end tidal respiration and the regional CO2 partial pressure value are not same temperature values, to modify the CO2 partial pressure gap value in accordance with the temperature difference between the standard temperature and the actual body temperature of the subject to provide an accurate indication of the CO2 gap.
Also, while the present invention has been described in connection with the measurement of CO2 partial pressures, it will be appreciate that it may be used in connection with other gases of interest, such as oxygen. And, while the use of arterial CO2 partial pressures have been described, as noted in the introduction portion of this specification, it is also possible to use venous CO2 partial pressures.
It is recognized that other equivalents, alternatives, and modifications aside from those expressly stated, are possible and within the scope of the appended claims.
|Cited Patent||Filing date||Publication date||Applicant||Title|
|US6029076 *||Mar 18, 1994||Feb 22, 2000||Instrumentarium Corp.||Remote sensing tonometric catheter method|
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|1||Gastric Intramucosal pH: A noninvasive Method for the Indirect measurement of Tissue Oxygenation, Cinda H. Clark, RN, BSN, and Guillermo Gutierrez, MD, PhD, American Journal of Critical Care,vol. 1, No. 2, (1992) 2:53-60.|
|2||The Arterial to End-Tidal Carbon Dioxide Gradient increases with Uncorrected but Not with Temperature-corrected Paco2Determination during Mild to Moderate Hypothermia, Christian Sitzwohl, MD, et al. Anesth. Analg. (1998) 86:1131-6.|
|3||The role of gut mucosal hypoperfusion in the pathogenesis of post-operative organ dysfunction, M. G. Mythen, A. R. Webb, Intensive Care Medicine (1994) 20:203-209.|
|Citing Patent||Filing date||Publication date||Applicant||Title|
|US6997880 *||Feb 28, 2002||Feb 14, 2006||Oridion Medical 1987, Ltd.||Waveform interpreter for respiratory analysis|
|US7909769 *||Jan 12, 2009||Mar 22, 2011||Cardiac Pacemakers, Inc.||Carbon dioxide and activity monitoring|
|US20020082511 *||Feb 28, 2002||Jun 27, 2002||Ephraim Carlebach||Waveform interpreter for respiratory analysis|
|US20090131775 *||Jan 12, 2009||May 21, 2009||Qingsheng Zhu||Carbon dioxide and activity monitoring|
|WO2011027182A1||Sep 1, 2010||Mar 10, 2011||Domokos Boda||Tonometric device for examining respiratory insufficiency and regional tissue perfusion failure|
|U.S. Classification||600/345, 600/353, 600/309, 600/347, 600/364|
|Cooperative Classification||A61B5/1495, A61B5/1473, A61B5/14542, A61B5/412|
|European Classification||A61B5/1473, A61B5/1495, A61B5/145N, A61B5/41D|
|Oct 13, 1999||AS||Assignment|
Owner name: INSTRUMENTARIUM CORP., FINLAND
Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNORS:HOLTE, BO;MYTHEN, MICHAEL;REEL/FRAME:010304/0091
Effective date: 19981228
|Oct 27, 2004||REMI||Maintenance fee reminder mailed|
|Nov 5, 2004||SULP||Surcharge for late payment|
|Nov 5, 2004||FPAY||Fee payment|
Year of fee payment: 4
|Oct 20, 2008||REMI||Maintenance fee reminder mailed|
|Apr 10, 2009||LAPS||Lapse for failure to pay maintenance fees|
|Jun 2, 2009||FP||Expired due to failure to pay maintenance fee|
Effective date: 20090410